Antipsychotic Studied as Potential Therapy for BPD

A new study published in AJP in Advance provides evidence for the use of quetiapine—a second-generation antipsychotic indicated for the treatment of schizophrenia and bipolar disorder—as a potential therapy for borderline personality disorder (BPD).

A research team led by Donald Black, M.D., vice chair of education and a professor of psychiatry at the University of Iowa Carver College of Medicine, compared the efficacy and tolerability of low and moderate dosages of extended-release quetiapine in adults with BPD.

“A variety of psychotherapies has been developed [to treat BPD], and while research on the use of medication is ongoing, no drug has been approved in the United States or elsewhere for its treatment,” the researchers pointed out. “This study was designed to provide a rigorous test of extended-release (ER) quetiapine in the treatment of borderline personality disorder.”

According to the researchers, second-generation antipsychotics have been the medications most intensively studied for the treatment of BPD, but randomized, controlled trials of aripiprazole, olanzapine, and ziprasidone have produced mixed results. Only five studies, which have all shown promising results, have investigated the effectiveness of the atypical antipsychotic quetiapine in treating BPD symptoms. However, the researchers noted, these studies involved small sample populations and focused on specific symptoms of BPD—not general symptomatology of the illness.

To expand upon the findings generated from previous research, in the current study Black and colleagues randomly assigned 95 participants aged 18 to 45 who met DSM-IV criteria for BPD to receive a low (150 mg/day) or moderate (300 mg/day) dosage of quetiapine-ER or placebo for eight weeks. The Zanarini Rating Scale for Borderline Personality Disorder and the Modified Overt Aggression Scale were used to analyze changes in BPD symptoms.

The results showed that among the participants who completed the study, 82 percent of individuals receiving low-dosage quetiapine-ER had significant improvements in BPD symptoms such as cognitive disturbance, disturbed relationships, and aggression, compared with 48 percent in the placebo group. Effectiveness of moderate dosages was somewhat more effective than placebo but the difference did not reach statistical significance, thus suggesting that the lower dosage is the optimal one for most patients. However, time to response—defined as a reduction of at least 50 percent on the Zanarini scale—was significantly shorter in both low- and moderate-dosage groups, compared with placebo.

In regard to drug safety, participants taking the 300 mg dosages were more likely to experience adverse events and discontinue the study than were participants in the other two groups. The most frequently cited adverse events associated with the drug were sedation, change in appetite, and dry mouth.

“This study joins a growing body of evidence showing that a relatively brief course of quetiapine can provide clinically meaningful benefit to borderline patients,” the researchers said.

“Evidence-based practice guidelines for BPD throughout the United States, Europe, and Australia all agree that the primary, or core, treatment for BPD is psychotherapy and that medications can be useful as symptom-targeted adjunctive components of treatment, usually in relatively low doses for a time-limited period,” John Oldham, M.D., told Psychiatric News. Oldham is chief of staff at the Menninger Clinic and professor and executive vice chair of the Menninger Department of Psychiatry at Baylor College of Medicine and was not involved with the study.

He noted as well that recent studies emphasize the potential benefit of both mood stabilizers and antipsychotics in treating BPD. “This study is consistent with these trends in the literature,” said Oldham, who was cochair of the DSM-5 Personality and Personality Disorders Work Group.

As for Black and colleagues, they emphasized that while quetiapine was effective in treating many symptoms of BPD in their study, adverse effects associated with the drug must be taken into consideration when deciding whether to use it. They said that their findings point to a need to conduct more studies to confirm the efficacy of quetiapine—both extended- and immediate-release forms—in treatment for BPD.

Funding for the study was provided by AstraZeneca, which makes the Seroquel brand of quetiapine. ■

An abstract of “Comparison of Low and Moderate Dosages of Extended-Release Quetiapine in Borderline Personality Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial” can be accessed here.